Many additives for food, cosmetic, personal care and household products and the products into which they are incorporated are light sensitive owing to the ability of such additives to absorb radiation from UV and/or visible light. Such products and additives include sunscreens, organic colorants, dyes, antioxidants, fragrances, flavor ingredients, etc. These compounds can be elevated to a higher energy level (excited state) upon absorption of radiation. As such, they are more reactive than in their normal or ground state and will readily react with other molecules or breakdown into lower energy degradation products. The consequence of these reactions is a significant, if not complete, loss of product integrity, color loss, malodor, viscosity changes etc. of the products into which they are formulated. The probability of reaction or decomposition is directly related to the length of time the molecules remain in the excited state.
One method of addressing light sensitivity is through the use of light, especially UV light, absorbing chromophores; however, these do not block all light nor potential degradation pathways for photosensitive compounds. Another approach is through the quenching of excited chromophores. Quenching of excited chromophores reduces the lifetime of excited states thereby reducing the side reactions of excited state intermediates. Both methods result in some improvement in shelf life/shelf stability for formulated products. It would be desirable and beneficial to be able to combine UV-light absorbing capability with the ability to quench the excited state within a single molecule.
Achieving photostable sun and skin care formulations is a huge challenge to the formulator because of inherent instabilities of certain organic compounds, especially certain sunscreens like [1-3] (4-tert-butyl-4′-methoxy-dibenzoylmethane, Avobenzone, a UV-A sunscreen; antioxidants like natural Tocopherols and Carotenoids; fragrances such as Vanillin; colorants such as Guaiazulene; retinoids; water-soluble dyes; etc. Currently available photostabilizers satisfy the need to stabilize photosensitive compounds mostly in the acidic pH range but are unable to effectively reduce photo-fragmentation under UV-exposure when the formulation pH is basic or near neutral.
Topical sunscreen compositions are commonly used during outdoor work or leisure as a means for providing protection of exposed skin against acute and chronic adverse effects of solar radiation such as sunburn, cancer and photo-aging. Many effective sunscreen preparations are sold commercially and/or are described in the cosmetic and pharmaceutical literature. In general sunscreen preparations are formulated as creams, lotions, spray or oils containing, as the active agent, an ultra violet radiation absorbing or blocking compound. The sunscreen functions by absorbing or blocking ultra-violet radiation preventing its penetration into the skin. Although sunscreens do prevent erythema and are recommended to be used as part of safe-sun practices, current research suggests that photoprotection is also needed to reduce skin damage (K M Hanson and R T Clegg, Bioconvertible vitamin antioxidants improve sunscreen photoprotection against UV-induced reactive oxygen species, J Cosmet Sci, 54:589-598, 2003).
Organic sunscreens are classified into UV-A filters, UV-B filters or broad spectrum filters (UV-A and UV-B functionality in a single molecule) depending on the type of radiation they absorb. UV-A sunscreens absorb radiation in the 320 to 400 nm regions of the ultra violet spectrum and UV-B sunscreens absorb radiation in the 290 to 320 nm regions of the ultra violet spectrum (See Sunscreens, Regulations and Commercial Development, Third Edition, Nadim A. Shaath, Ed., Taylor & Francis, 2005). Broad-spectrum sunscreens (UV-A and UV-B functionality) absorb radiation in the 290 to 400 nm region of the ultra violet spectrum and have two maximums, one in the UV-B region and the other in the UV-A region. Representative references relating to UV sunscreens include Gonzalez et. al.—U.S. Pat. No. 7,186,404; Aust et. al.—U.S. Pat. No. 7,175,834; Roseaver et. al.—U.S. Pat. No. 7,172,754; Simoulidis et. al.—U.S. Pat. No. 7,175,835; Mongiat et. al.—U.S. Pat. No. 7,101,536; Maniscalco—U.S. Pat. No. 7,078,022; Chaudhuri et. al.—U.S. Pat. No. 6,165,450; Forestier et. al. U.S. Pat. No. 5,175,340; and Wang et. al. U.S. Pat. No. 5,830,441.
Unfortunately, some of the highly chromophoric monomeric organic compounds employed in sunscreen compositions are not photostable and the protection they may otherwise provide against sun damage is lost after only a short period of time. For example, Avobenzone, a UV-A sunscreen, is generally photo-unstable and, while certain combinations of sunscreens are found to provide broader sun protection, the photo-instability of Avobenzone increases significantly when combined with other sunscreen actives such as octyl methoxycinnamate (a UV-B organic sunscreen) thereby resulting in an even shorter period of protection. This is surprising since octyl methoxycinnamate (OMC) has been regarded as relatively photostable in accordance with most studies; however, the absorption maxima of Avobenzone (about 360 nm) and OMC (about 310 nm) do not overlap sufficiently to allow directly excited singlet-singlet energy transfer to occur. Such an energy transfer from one excited triplet-state to another is possible provided the absorption energy levels of each component sufficiently overlap to allow for the transfer and, hence, an additive effectiveness.
Octocrylene, a UV-B absorber, has found widespread use in sunscreen formulations because of its photostability and perceived non-irritant and non-sensitizer properties, Octocrylene has been found to be an excellent photostabilizer for Avobenzone; however, recent studies have reported many instances of contact allergy (CA) and photocontact allergy (PCA) to octocrylene (A Bennàssar, R Grimalt, C Romaguera, J Vilaplana, “Two cases of photocontact allergy to the new sun filter octocrylene”, Dermatology Online Journal, 15(12):14, 2009; D Pascoe, L Moreau and D Sasseville, “Emergent and unusual allergens in cosmetics”, Dermatitis, 21(3):127-137, 2010; D Delplace and A Blondeel A, “Octocrylene: really non-allergenic?”, Contact Dermatitis, 54(5):295, 2006).
A recent study based on in vitro approaches was performed to demonstrate that photostability is an essential requirement to protect against UVA-induced genetic and dermal alterations (L Marrot, J P Belaïdi, F Lejeune, J R Meunier, D Asselineau, F Bernard, “Photostability of sunscreen products influences the efficiency of protection with regard to UV-induced genotoxic or photoaging-related endpoints”, British J Dermatol, 151(6):1234-1244, 2006). The protection afforded by two sunscreen products, differing with regard to their photostability, was studied by the authors using biological markers related to the genotoxic or photoaging impact of UVA or simulated solar UV radiation (UV-SSR). Comet assay was used to assess direct DNA breakage, photo-oxidized purines and lomefloxacin-induced DNA breaks in nuclei of normal human keratinocytes in culture. In similar conditions, detection of p53 accumulation was performed. Results showed that photo-unstable sunscreen products causes: (a) formation of sunburn cells; (b) DNA damage with increased formation of pyrimidine dimers; (c) dermal alterations with superficial fibroblasts; higher dose causes destruction of dermal fibroblasts and (d) formation of higher level of MMP-1
Various techniques for stabilizing UV absorbent compositions are known. Representative disclosures in this area include Forestier et. al.—U.S. Pat. No. 5,567,418, U.S. Pat. No. 5,538,716, and U.S. Pat. No. 5,951,968; Deflandre et. al.—U.S. Pat. No. 5,670,140; Chaudhuri—U.S. Pat. No. 8,003,082, 7,150,876, 6,831,191, 6,602,515, 7,166,273, 6,936,735, 6,831,191, and 6,699,463; Chaudhuri et. al.—U.S. Pat. No. 7,150,876; and Bonds et. al. U.S. Pat. No. 6,962,692. In an effort to address some of the shortcomings of typical sunscreen compositions, certain manufacturers have added antioxidants. Antioxidants are believed to provide protection from free-radical damage by quenching or sequestering free radicals generated by UV exposure. Photo-protective products combining sunscreens and an antioxidant or antioxidant mixtures have been touted as providing increased efficacy and safety relative to UV exposure (S R Pinnell, “Cutaneous Photodamage, Oxidative Stress; and Topical Antioxidant Protection”, J Am Acad Dermatol, 48: 1-19, 2003). To be an effective quencher, it is believed that the antioxidant must be present in an adequate concentration at the site of free radical generation. However, since antioxidants are used in relatively low concentrations and are a separate ingredient, they may not be available at the site of free radical generation. Consequently, the level of skin protection may be reduced and, oftentimes, less than desired.
While the general use of antioxidants in sunscreen formulations is advocated, the fact that many of these compounds not only function as antioxidants, but intrinsically have pro-oxidant action as well, especially in the presence of transition metals, is oftentimes overlooked or disregarded. (See e.g., “Role of Antioxidants in Sun Care Products” by R. Chaudhuri in Sunscreens, N A Shaath, editor, Taylor and Francis, p 603-638, 2005). Pro-oxidant action is seen with even well-known antioxidants such as vitamin C (ascorbate), vitamin E (tocopherols), glutathione and proanthocyanidins (from pine and grape). The pro-oxidant activity of vitamin C results from the reduction of Fe3+ to Fe2+ and its reaction with H2O2 to generate OH radicals. Pro-oxidant effects are not unique to vitamin C: they can be demonstrated with many reducing agents, including vitamin E, glutathione and several plant phenolic compounds, in the presence of transition metal ions. Thus, if vitamin C's pro-oxidant effects are relevant, the pro-oxidation effects of these other reductants may also be expected to occur.
Ideally, sun and skin care products should be such that no or minimal photochemical instability or photosensitizing transformations of its components occur within the formulation or on the skin. Photochemical stability is indeed the most important characteristic of an effective UV filter since the light-induced degradation of the sunscreen agent not only reduces its photoprotective efficacy, but can also promote phototoxic or photoallergic contact dermatitis (V A DeLeo, S M Suarez, M J Maso, “Photoallergic contact dermatitis”, Arch. Dermatol. 128:113-118, 1992; R. Haywood, P Wardman, R Sanders & C Linge, “Sunscreens inadequately protect against ultraviolet-A-induced free radicals in skin: implications for skin aging and melanoma?”, J. Invest. Dermatol, 121:862-868, 2003). This is not only true for sunscreens; but also true for other formulation ingredients. Photo-instability can result in the formation of singlet oxygen species, thereby causing damage to biomolecules such as DNA, proteins, lipids, etc. (J L Ravanat, G R Martinez, M H Medeiros, P Di Mascio and J Cadet, “Mechanistic aspects of the oxidation of DNA constituents mediated by singlet molecular oxygen”, Arch. Biochem Biophys, 423:23-30, 2004; J L Ravanat, S Sauvaigo, S Caillat, G R Martinez, M H G Medeiros, P Di Mascio, A Favier and J Cadet, “Singlet oxygen-mediated damage to cellular DNA determined by the comet assay associated with DNA repair enzymes”, Biol. Chem. 385: 17-20, 2004; M J Davies, “Reactive species formed on proteins exposed to singlet oxygen”, Photochem. Photobiol. Sci. 3:17-25, 2004; I. Tejero I, A Gonzalez-Lafont, J M. Lluch and L A Eriksson, “Photo-oxidation of lipids by singlet oxygen: a theoretical study”, Chem Phys Lett, 398:336-342, 2004; C Kielbassa and B. Epe, “DNA damage by UV and visible light and its wavelength dependence”, Methods Enzymol, 319:436-445, 2000)
Since Avobenzone is a very desirable UV-A sunscreen component of many sunscreen products and its photo-instability is known, considerable effort has been devoted to studies of these instabilities (C A Bonda, “The photostability of organic sunscreens: A review” In: Shaath N A, ed. Sunscreens, New York, Taylor & Francis, 2005; 321-349). Furthermore, it is believed that there are more than 170 issued US patents that are related in one way or another to the photo-stabilization of avobenzone (dibenzoylmethane). Representative patent publications include those set forth in Table 1.
TABLE 118,003,082Photostable organic sunscreen composition27,544,350Method of decreasing the UV light degradation ofpolymers37,186,404Photostable sunscreen compositions and methodsof stabilizing46,444,195Sunscreen compositions containing a dibenzoylmethanederivative56,426,428UV-photoprotective dibenzoylmethane compositionscomprising photostabilizing amounts ofbenzalmalonate silanes66,312,673Photostabilized sunscreen compositions comprisingdibenzoylmethane compounds and benzylidenecamphor-substituted silanes/organosiloxanes76,290,938Sunscreen compositions86,224,854UV protection compositions96,174,517Compositions containing a dibenzoylmethane derivativeand a titanium oxide nanopigment, and uses106,071,501Photostable UV protection compositions115,976,513UV protection compositions125,972,316UV protection compositions135,968,485UV protection compositions145,951,968UV-photoprotective dibenzoylmethane compositionscomprising photostabilizing amounts ofbenzalmalonate silanes155,788,954Hydrating skin care and sunscreen compositioncontaining dibenzoylmethane derivative, E.G., parsol1789, and C12, C16, C18 branched chainhydroxybenzoate and/or C12, C16, branched chainbenzoate stabilizers/solubilizers165,783,173Stable sunscreen composition containingdibenzoylmethane derivative, E.G., PARSOL 1789, andC12, C16, C18 branched chain hydroxybenzoate and/orC12, C16, branched chain benzoatestabilizers/solubilizers175,567,418Process for stabilizing 4-(1,1-dimethylethy)-4′methoxydibenzoyl-methane against UV radiation185,538,716Photostable cosmetic screening composition containinga UV-A screening agent and a(4-methoxybenzylidene)cyanoacetate
Among the various compounds that have been tested and evaluated, certain benzylidene malonate esters having antioxidant functionality have been identified as good photo-stabilizers for stabilizing photo-unstable compounds like sunscreens, antioxidants, dyes, vitamins, flavors, fragrance and other food, cosmetic and health and beauty aid product ingredients. Representative disclosures in this area are set forth in the Table 2.
TABLE 218,003,082Photostable organic sunscreen composition27,166,273Photo stable organic sunscreen compositions37,150,876Methods for stabilizing ingredients within cosmetics,personal care and household products46,936,735Photostable cationic organic sunscreen compounds andcompositions obtained therefrom56,831,191Photo stable organic sunscreen compounds withantioxidant properties and compositions obtainedtherefrom66,699,463Photostable cationic organic sunscreen compounds withantioxidant properties and compositions obtainedtherefrom76,602,515Photo stable organic sunscreen compounds withantioxidant properties and compositions obtainedtherefrom
Antioxidant, photo-stabilizer compounds described in the above referenced patent literature are commercially available under the trade names Oxynex® ST (Diethylhexyl syringylidene malonate) and Oxynex® ST Liquid (blend of Oxynex® ST and caprylic/capric triglycerides). These have been shown to stabilize Avobenzone and other photo-unstable compounds. Unfortunately, Oxynex® ST is not an effective broad spectrum antioxidant and its effectiveness drops significantly when exposed to UV irradiation above 40 Joules/cm2.
Another class of ingredients of cosmetic and health and beauty aid products that manifest photo-instability is the retinoids. These compounds are an especially important class of drugs used to treat a variety of health conditions including acne, photoaging, psoriasis, ichthyosis, hair loss, and various cancers and generally consist of four isoprenoid units joined in a head to tail manner. All retinoids may be derived from a monocyclic parent compound containing five carbon-carbon double bonds and a functional group at the terminus of the acyclic portion. The retinoids include Vitamin A (retinol) and its natural and synthetic derivatives, analogues, and metabolites that exhibit biological activity qualitatively similar to retinol. Particularly important retinoids include retinol, retinyl esters, retinal, and isomers of retinoic acid, including all-trans-retinoic acid (tretinoin) and cis-isomeric retinoic acids, e.g., 13-cis-retinoic acid (isotretinoin) and 9-cis-retinoic acid. The naturally occurring retinoids are essential for many of life's processes including vision, reproduction, metabolism, differentiation, bone development, and pattern formation during embryogenesis.
Retinoids, however, are extremely sensitive to UV light, air, and oxidizing agents due to their high degree of unsaturation. For example, tretinoin must be stored under an atmosphere of inert gas (e.g., argon) in the dark at <−20° C. to preserve its integrity and biological activity. While solutions of tretinoin in pure organic solvents are stable when stored in the dark, aqueous solutions deteriorate quickly. Retinoids are lipophilic. For example, tretinoin is practically insoluble in water, slightly soluble in ethanol (3 mg/ml) and chloroform, sparingly soluble in ether, and soluble in methylene chloride and dimethyl sulfoxide (40 mg/ml).
Banda (U.S. Pat. No. 6,551,605) has shown that certain diesters of naphthalene dicarboxylic acid are good solvents for retinoids. For example, isotretinoin is soluble in the diethylhexyl diester of 2,6-naphthalene-dicarboxylic acid at approximately 6.7 mg/ml, and tretinoin is soluble in the same diester at approximately 5.6 mg/ml. While solutions of tretinoin in pure organic solvents are stable when stored in the dark, aqueous solutions deteriorate quickly. A solution of a retinoid such as tretinoin or isotretinoin in a diester of naphthalene dicarboxylic acid has been shown to be quite stable if kept in the dark.
Di- or poly-esters of naphthalene have been claimed to be effective solubilizers and stabilizers for a wide variety of photosensitive compounds. Representative disclosures in this regard as set forth in the Table 3.
TABLE 317,799,317Photostabilizers, UV absorbers, and methods ofphotostabilizing compositions26,518,451Diesters of naphthalene dicarboxylic acid36,444,195Sunscreen compositions containing a dibenzoylmethanederivative46,284,916Diesters of naphthalene dicarboxylic acid56,180,091Compositions containing diesters or polyesters ofnaphthalene dicarboxylic acid and methods for impartinghair gloss and to provide hair color and hair dyestabilization66,129,909Compositions containing diesters or polyesters ofnaphthalene dicarboxylic acid and methods for impartinghair gloss and to provide hair color and hair dyestabilization76,126,925Photostable sunscreen compositions containingdibenzoylmethane derivative, e.g., PARSOL ® 1789,and diesters of naphthalene dicarboxylic acidphotostabilizers and enhancers of the sun protectionfactor (SPF)86,113,931Clear formulations containing diesters or polyesters ofnaphthalene dicarboxylic acid95,993,789Photostable sunscreen compositions containingdibenzoylmethane derivative, E.G., parsol ® 1789, anddiesters or polyesters of naphthalene dicarboxylic acidphotostabilizers and enhancers ofthe sun protection factor (SPF)105,849,273Skin care and sunscreen composition containingdibenzoylmethane derivative, e.g., parsol ® 1789, andC12, C16, C18 branched chain hydroxybenzoate and/orC12, C16, C18 branched chain benzoatestabilizers/solubilizers
Despite these advances, there is still a huge need and demand for photo-stabilizers that are able to stabilize photosensitive ingredients used in and within foods, cosmetics, personal care and household products that are more effective and more forgiving than the aforementioned compounds. The shortcomings of presently available photostabilizers include, but not limited to:                Hydrolytic instability most likely arising from the presence of one or more ester functionalities, the later limiting their use in basic pH compositions/conditions. Also, esters in general are more hydrolytically unstable than their non-ester counter parts, for example ketones,        Presence of color and formation of intense yellow/orange coloration in basic pH due to the presence of phenolic hydroxyl group or groups. Non-phenolic stabilizers are also highly colored, for example, Octocrylene and octocrylene derivatives, namely, Polycrylene® (Viscous oily liquid, Polyester-8, available from Hallstar), Solastay™ S1 (Viscous oily liquid, Ethylhexyl methoxycrylene, available from Hallstar).        Indications of contact allergy (CA) and photocontact allergy (PCA) to Octocrylene, a widely used UV-B organic sunscreen and an excellent stabilizer of Avobenzone.        
Loss of effectiveness when exposed to UV dose of >40 Joules/cm2, as found with, for example, Corapan® TQ (Diethyhexyl 2,6 naphthalate, Symrise), Oxynex® ST (Diethyhexyl syringylidene malonate, EMD Chemicals),                Instability of photostabilizers having phenolic functionality in basic pH due to the formation of phenolate anion.        